Methods for improving stent retention on a balloon catheter

ABSTRACT

A method of crimping a stent on a balloon of a catheter assembly is provided. A polymeric stent is disposed over a balloon in an inflated configuration. The stent is crimped over the inflated balloon to a reduced crimped configuration so that the stent is secured onto the balloon. The balloon wall membrane is wedged or pinched between the strut elements of the stent for increasing the retention of the stent on the balloon.

TECHNICAL FIELD

This invention relates to methods of crimping or mounting a stent on aballoon of a catheter assembly.

BACKGROUND

A stent, as illustrated in FIG. 1, is an intravascular prosthesis thatis delivered and implanted within a patient's vasculature or otherbodily cavities and lumens by a balloon catheter. For example, stentscan be used in percutaneous transluminal coronary angioplasty (PTCA) orpercutaneous transluminal angioplasty (PTA). Conventional stents andcatheters are disclosed by U.S. Pat. Nos. 4,733,665, 4,800,882,4,886,062, 5,514,154, 5,569,295, and 5,507,768. In advancing a stentthrough a body vessel to a deployment site, the stent must be able tosecurely maintain its axial as well as rotational position on thedelivery catheter without translocating proximally or distally, andespecially without becoming separated from the catheter. Stents that arenot properly secured or retained to the catheter may slip and either belost or be deployed in the wrong location. The stent must be “crimped”in such a way as to minimize or prevent distortion of the stent and tothereby prevent abrasion and/or reduce trauma to the vessel walls.

Generally, stent crimping is the act of affixing the stent to thedelivery catheter or delivery balloon so that it remains affixed to thecatheter or balloon until the physician desires to deliver the stent atthe treatment site. Current stent crimping technology is sophisticated.Examples of such technology which are known by one of ordinary skill inthe art include a roll crimper; a collet crimper; and an iris orsliding-wedge crimper. To use a roll crimper, first the stent is slidloosely onto the balloon portion of the catheter. This assembly isplaced between the plates of the roll crimper. With an automated rollcrimper, the plates come together and apply a specified amount of force.They then move back and forth a set distance in a direction that isperpendicular to the catheter. The catheter rolls back and forth underthis motion, and the diameter of the stent is reduced. The process canbe broken down into more than one step, each with its own level offorce, translational distance, and number of cycles. This processimparts a great deal of shear to the stent in a direction perpendicularto the catheter or catheter wall. Furthermore, as the stent is crimped,there is additional relative motion between the stent surface and thecrimping plates.

The collet crimper is equally conceptually simple. A standarddrill-chuck collet is equipped with several pie-piece-shaped jaws. Thesejaws move in a radial direction as an outer ring is turned. To use thiscrimper, a stent is loosely placed onto the balloon portion of acatheter and inserted in the center space between the jaws. Turning theouter ring causes the jaws to move inward. An issue with this device isdetermining or designing the crimping endpoint. One scheme is toengineer the jaws so that when they completely close, they touch and acenter hole of a known diameter remains. Using this approach, turningthe collet onto the collet stops crimps the stent to the known outerdiameter. While this seems ideal, it can lead to problems. Stent strutshave a tolerance on their thickness. Additionally, the process offolding non-compliant balloons is not exactly reproducible.Consequently, the collet crimper exerts a different amount of force oneach stent in order to achieve the same final dimension. Unless thisforce, and the final crimped diameter, is carefully chosen, thevariability of the stent and balloon dimensions can yield stent orballoon damage.

In the sliding wedge or iris crimper, adjacent pie-piece-shaped sectionsmove inward and twist, much like the leaves in a camera aperture. Thiscrimper can be engineered to have two different types of endpoints. Itcan stop at a final diameter, or it can apply a fixed force and allowthe final diameter to float. From the discussion on the collet crimper,there are advantages in applying a fixed level of force as variabilityin strut and balloon dimension will not change the crimping force. Thesliding wedges impart primarily normal forces. As the wedges slide overeach other, they impart some tangential force. Lastly, the sliding wedgecrimper presents a nearly cylindrical inner surface to the stent, evenas it crimps. This means the crimping loads are distributed over theentire outer surface of the stent.

All current stent crimping methods were developed for all-metal stents.Stent metals, such as stainless steel, are durable and can take abuse.When crimping is too severe, it usually damages the underlying balloon,not the metal stent. But polymeric stents present different challenges.A polymer stent requires relatively wider struts than metal stents so asto provide suitable mechanical properties, such as radial strength. Atthe crimping stage, less space is provided between the struts which canresult in worse stent retention than a metallic stent. Moreover, the useof high processing temperature during the crimping process to enhancestent retention may not be possible as a polymeric stent may have aglass transition temperature generally equivalent to the glasstransition temperature of the balloon. Higher processing temperaturesmay cause the stent to lose some of its preferred mechanical properties.

The present invention provides a novel method of crimping a stent, morespecifically a polymeric stent on an expandable member or a balloon.

SUMMARY

In accordance with one embodiment, a method of crimping a stent on aballoon of a catheter assembly is provided, comprising: providing apolymeric stent disposed over a balloon in an inflated configuration;and crimping the stent over the inflated balloon to a reduced crimpedconfiguration so that the stent is secured onto the balloon. In someembodiments, the act of providing comprises inserting a balloon in acollapsed configuration into a stent; and expanding the balloon to theinflated configuration, wherein the inflated configuration is equal toor less than the intended expansion configuration of the balloon. Insome embodiments, the inflated configuration is a configuration whichprovides for a membrane or wall of the balloon to protrude into gapsbetween structural elements of the stent. As a result, subsequent tocrimping the stent on the balloon, a membrane or wall of the balloon ispinched or wedged between the structural elements of the stent. Duringthe crimping process, the pressure in the balloon can be controllablyreleased by a valve. In some embodiments, the stent is not a metallicstent. In some embodiments, the stent is a biodegradable polymericstent. In some embodiments, the stent is a biodegradable polymeric stentwith or without a biodegradable metallic component.

In accordance with another embodiment, a method of crimping a stent on aballoon, is provided comprising the following acts in the order aslisted: (a) providing a stent disposed over a balloon in an inflatedconfiguration; (b) crimping the stent to a first reduced diameter; (c)at least partially deflating the balloon; (d) inflating the balloon toat least an inner diameter of the stent; and (e) crimping the stent to asecond reduced diameter. The second reduced diameter can be the finalcrimped diameter.

DESCRIPTION OF FIGURES

The figures have not been drawn to scale and portions thereof have beenunder or over emphasized for illustrative purposes.

FIG. 1 illustrates an example of a stent;

FIGS. 2A, 2B1, 2B2, 2C, 2D, and 2E (collectively referred to as FIG. 2)illustrate methods for crimping a stent on a balloon of a catheter;

FIG. 3 illustrates an embodiment of the end result of a stent/catheterassembly produced in accordance with a method of the invention;

FIGS. 4A and 4B are photographs of a stent crimped on a balloon inaccordance with an embodiment of the invention; and

FIG. 5 is a graph illustrating the result of the Example.

DESCRIPTION

The stent crimping methods are suitable to adequately and uniformlycrimp a balloon expandable stent onto a balloon or expandable member ofa catheter assembly. The embodiments of the invention are alsoapplicable to self-expandable stents and stent-grafts. In oneembodiment, the method of the present invention is particularly directedto crimping of a biodegradable, polymeric stent on a balloon of acatheter assembly. A biodegradable polymer stent has many advantagesover metal stents, including the ability to be placed in the body onlyfor the duration of time until the intended function of the stent hasbeen performed. However, retention of a polymer stent has been proven tobe more challenging than that of a metallic stent. Polymer stents canrequire wider struts than metal stents so as to provide suitablemechanical properties, such as radial strength, for the stent. At thecrimping stage, less space is provided between the struts which canresult in worse stent retention than a metallic stent. Moreover, the useof high processing temperature during the crimping process to enhancestent retention may not be possible as a polymeric stent may have aglass transition temperature generally equivalent to, or lower than theglass transition temperature of the balloon. Higher processingtemperatures may cause the polymeric stent to lose some of its preferredmechanical properties.

FIG. 2A illustrates an expandable member, such as a balloon 10,integrated at a distal end of a catheter assembly 12. In someembodiments, the balloon 10 is intended to include any type of enclosedmember such as an elastic type member that is selectively inflatable todilate from a collapsed configuration to a desired and controlledexpanded configuration. The balloon 10 should also be capable of beingdeflated to a reduced profile or back to its original collapsedconfiguration. The balloon 10 can be made from any suitable type ofmaterial and can be of any thickness so long as the ability to crimp thestent onto the balloon and optimum performance capabilities of theballoon are not adversely compromised. Performance properties include,for example, high burst strength, good flexibility, high resistance tofatigue, an ability to fold, and ability to cross and re-cross a desiredregion of treatment or an occluded region in a bodily lumen, and a lowsusceptibility to defects caused by handling and crimping, among otherpossibilities.

The balloon is illustrated in FIG. 2A in a collapsed configuration. Thecollapsed configuration can be the configuration that is conventionallyused during the process of crimping of a stent on a balloon. The balloon10 includes no liquid or gas in the internal chamber of the balloon 10and includes regions where the balloon material is folded over givingthe balloon a crease-like appearance. Such collapsed configuration canbe the configuration of introduction and navigation of the balloon 10 inthe vascular system of a patient.

As illustrated in FIG. 2B1, a stent 14 is positioned over the balloon10. The stent 14 is illustrated to have struts 16 separated by gaps 18(as can also be seen in FIG. 1). In some embodiments, the diameter ofthe stent 14 as positioned over the collapsed balloon 10 is much largerthan the collapsed diameter of the balloon 10. In some embodiments, asillustrated in FIG. 2B2, the diameter of the stent 14 is large enough sothat an operator is capable of slipping the stent 14 over the balloon 10with minimal gap or space between the balloon 10 and the stent 14. Theballoon 10 can be inflated to a crimp inflation state before beingplaced into a crimping device 20 (FIG. 2C) or after being placed intothe crimping device 20. The crimp inflation state is a state greaterthan the collapsed configuration and is a state equal to or less thanthe intended expansion configuration or use state. The intendedexpansion configuration is defined as inflation of a balloon to adiameter or size within the range of its intended use or design. Theintended expanded configuration is provided by the manufacturer of theballoon or can be determined by one having ordinary skill in the art andis intended to include the range of diameter of use or the range ofpressure to be applied for the planned performance of the balloon. Insome embodiments, the balloon's intended use state is up to thethreshold inflated configuration where the balloon becomes damaged ordisapproved for use if the balloon was inflated more.

The balloon 10 can be inflated by application of a fluid or a gas. Thetemperature of the fluid or gas can be adjusted to other than ambient orroom temperature. In one embodiment, a heated fluid or gas is used. Insome embodiments, heated can be defined as above 25 deg. C. In someembodiments, the temperature can be below 200 deg. C., or alternativelybelow 150 deg. C., or alternatively below 100 deg. C., or alternativelybelow 75 deg. C. In some embodiments, the temperature can be between 25deg. C. and 100 deg. C. In some embodiments, the temperature is equal toor above the glass transition temperature (Tg) of a polymer of the stentbody or a polymer of the stent coating (if applicable). In someembodiments, the temperature is equal to or above Tg but less thanmelting temperature of the of a polymer of the stent body or a polymerof the coating. In some embodiments, a cooled or chilled fluid or gascan be used to inflate the balloon. Cooled can mean below 25 deg. C.Chilled can mean below 0 deg. C.

In some embodiments, the crimped inflation state can includehyper-inflation of the balloon. Over or hyper-inflation is defined asany diameter or size above the intended expanded configuration but lessthan a diameter or size which the balloon will be damaged or no longersuitable or its intended use. Balloon diameter tolerances depend on thetype of balloon and the material from which the balloon is made, amongother factors. The manufacturer of the balloon can provide suchinformation to a user, for example.

As illustrated in FIG. 2C, when the balloon 10 is inflated, it ispreferred for the balloon wall or membrane to protrude out, as shown byreference number 22, from the gaps 18 between the stent struts 16. Inone embodiment, the protrusion 22 should not extend beyond the outersurface of the struts 16. Alternatively, the protrusion 22 can extendbeyond the outer surface of the struts 16. This ensures that the balloonwall or membrane becomes adequately wedged, lodged, squeezed, or pinchedbetween the struts 16 when the crimping process is completed.

Next, as illustrated in FIG. 2D, the balloon 10 and the stent 14 areplaced in the crimping device 20. Again, the balloon 10 can be inflatedafter being placed in the crimping device. The stent 14 can bepositioned in the device 20 and held in place by application of pressurefrom the crimping device 20. The balloon 10 is then inserted within thestent 14. The balloon 10 is then inflated. The balloon 10 can beinflated to the inner diameter of the stent 14 or the diameter of thecrimping device 20. In some embodiments, the balloon 10 can radiallyexpand the stent 14 to a certain degree. The crimp device 20 thenapplies inward radial pressure to the stent 14 on the balloon 10.

The crimping device 20 can be any device used in the art. The stent 14positioned over the balloon 10 is crimped to a reduced balloon and stentconfiguration (reduced crimped configuration), as illustrated in FIG.2E. The reduced crimped configuration can be the final, desiredconfiguration (i.e., the configuration used to introduce the device intothe patient). Alternatively, reduced crimped configuration can be anintermediate configuration such that further crimping is needed. In oneembodiment, the stent 14 is reduced in diameter, the balloon 10 isdeflated (such as by application of a vacuum) and then re-inflated tothe inner diameter of the stent 14 or diameter of the crimper. This isfollowed by further application of pressure by the crimping device 20.The process of application of pressure by the crimper, deflation of theballoon, re-inflation of the balloon, and application of pressure can beperformed any number of times until the final, desired crimped state isachieved.

Crimping can be defined as the process of mounting, fastening orsecuring a stent on a balloon. The stent can be fixedly carried by theballoon but can be deployed by inflation and subsequent withdrawal ofthe balloon in order to be implanted at a target site, such as a regionof stenosis. The crimp process can include selectively, radiallycompressing or applying pressure for positioning a stent on a balloon ofa catheter assembly or an expandable delivery member of a catheterassembly. The compression or radial pressure during crimping can besegmented or uniform across the length and/or circumference of thestent. The application of pressure by the crimping device 20 can becontinuous or applied in an intermittent or step-wise fashion. In anintermittent embodiment, the balloon can be deflated and re-inflateduntil final crimp configuration has been achieved. In some embodiments,the crimping device can hold the pressure at the reduced crimpedconfiguration for duration of time prior to release of pressure. Theprocess of crimping can also include, unless otherwise specificallyindicated, modification made to the stent and/or balloon prior, duringor subsequent to the application of crimping pressure that are directedto retention of the stent on the balloon. For example, the balloon canbe coated before crimping to improve the retention of the stent on theballoon. In some embodiments, the balloon can be dipped into a fluid orsolvent such as acetone before sliding the stent on the balloon in orderto soften the balloon material. This makes it easy for the balloonmaterial to squeeze into the space between the struts or structuralelements. The solvents, such as acetone, may also partially dissolve thesurface of the stent or coating on the stent allowing for betteradhesion between the stent and the balloon. In some embodiments, asoftening fluid can be used that is a non-solvent for the stent or thecoating on the sent. By way of another example, a grip process can beconducted after crimping to further increase stent retention. An outersleeve restrains the crimped stent. Simultaneously, pressure and heatare applied to the stent-balloon section. Under this action, the balloonmaterial deforms slightly, moving in between the struts.

Reduced balloon configuration (i.e., reduced crimp configuration) is asize or diameter greater than the size or diameter of the balloon 10 inits collapsed configuration. In some embodiments, the measured reducedsize or diameter can be equivalent or generally equivalent to that ofthe collapsed configuration. Since the balloon 10 is pressurized by afluid or gas, a pressure release valve 24 is provided to allow releaseof pressure from the balloon 10 during the crimping process. During thecrimping process, the pressure release valve 24 will open to releasepressure when the compression pressure caused by the crimping is higherthan a set value of the valve 24. The release of the pressure iscontrolled so as to allow the crimper 20 to apply adequate pressure onthe stent 14 for fastening the stent 14 on the balloon 10. If too muchpressure is released from the balloon 10 during crimping, the stent 14may not be adequately crimped on the balloon 10. The set pressure valueof the valve depends on a variety of factors including the type ofcrimping device, stent, and balloon used. The calculation of the amountof applied pressure and preset valve pressure intake can be readilydetermined by one having skilled in the art.

As illustrated in FIG. 3, the balloon 10, in a reduced configuration,has the stent 14 tightly crimped thereon. Balloon folds 22 have beentightly lodged, squeezed, wedged or pinched between the struts 16 of thestent 14. As the stent 14 is crimped, the struts 16 are shifted orbrought closer together, causing the balloon wall or membrane 22 to bepinched between the struts 16. As for the end ring(s) of the stent 14,the balloon wall membrane 22 can be disposed between the structuralelements of the stent as well. FIGS. 4A and 4B are two photographs whichillustrate this crimping configuration in accordance to some embodimentof the present invention. As illustrated by the photographs, balloonwall or membrane is wedged between the structural elements of the stent.

In some embodiments, the stent 14 is arranged on the balloon 10 so thatan outside surface of the balloon 10 and an inside surface of the stent14 contact each other to form a combination of the balloon and stent. Insome embodiments, the outer surface of the balloon or the inner surfaceof a stent can include a coating such as an adhesive coating, a drugdelivery coating, a protective coating, a polymeric coating, a blockingagent or the like. The blocking agent is intended to reduce adhesionand/or friction between the stent 14 or a coating on the stent 14 andthe balloon 10.

The stent body itself is preferably made from a polymeric material suchas one or a combination of polymers. In some embodiments, such body canbe made from a combination of polymeric and metallic material(s). Insome embodiments, the stent is biodegradable. Both polymers and metallicmaterials can be biodegradable. In one preferred embodiment, the stentis completely or exclusively made from a polymeric material orcombination of polymeric materials, more specifically biodegradablepolymer(s). A polymeric stent can include some metallic components forallowing the stent to be viewed during the procedure; however, theamount of material is insignificant, does not impart any structuralfunction to the stent, or for viewing means only such that the stent isin essence made from a polymeric material or combination of polymers asis understood by one having ordinary skill in the art. In someembodiments, metallic stents are completely excluded from any of theembodiments of this invention. Metallic stents have a stent body (i.e.,struts or structural elements) made mostly or completely from a metallicmaterial such as an alloy. It should be noted that biodegradable isintended to include bioabsorbable, bioerodable, etc. unless otherwisespecifically indicated.

In some embodiments, the stent can include a drug coating. The coatingcan be a pure drug or combination of drugs. The coating can include apolymeric carrier of a single or multiple polymers. The coating can belayered as is understood by one of ordinary skilled in the art.

The stent or the coating can be made from a material including, but arenot limited to, poly(N-acetylglucosamine) (Chitin), Chitosan,poly(hydroxyvalerate), poly(lactide-co-glycolide),poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate),polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide),poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic acid),poly(D,L-lactide), poly(caprolactone), poly(trimethylene carbonate),polyester amide, poly(glycolic acid-co-trimethylene carbonate),co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules(such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronicacid), polyurethanes, silicones, polyesters, polyolefins,polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymersand copolymers other than polyacrylates, vinyl halide polymers andcopolymers (such as polyvinyl chloride), polyvinyl ethers (such aspolyvinyl methyl ether), polyvinylidene halides (such as polyvinylidenechloride), polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics(such as polystyrene), polyvinyl esters (such as polyvinyl acetate),acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides,polyethers, polyurethanes, rayon, rayon-triacetate, cellulose, celluloseacetate, cellulose butyrate, cellulose acetate butyrate, cellophane,cellulose nitrate, cellulose propionate, cellulose ethers, andcarboxymethyl cellulose. Another type of polymer based on poly(lacticacid) that can be used includes graft copolymers, and block copolymers,such as AB block-copolymers (“diblock-copolymers”) or ABAblock-copolymers (“triblock-copolymers”), or mixtures thereof.

Additional representative examples of polymers that may be especiallywell suited for use in fabricating or coating the stent include ethylenevinyl alcohol copolymer (commonly known by the generic name EVOH or bythe trade name EVAL), poly(butyl methacrylate), poly(vinylidenefluoride-co-hexafluororpropene) (e.g., SOLEF 21508, available fromSolvay Solexis PVDF, Thorofare, N.J.), polyvinylidene fluoride(otherwise known as KYNAR, available from ATOFINA Chemicals,Philadelphia, Pa.), ethylene-vinyl acetate copolymers, and polyethyleneglycol.

EXAMPLE 1.

A first polymer stent was crimped by in-house process. A second polymerstent was placed on a balloon and then inserted into the crimper. Thecrimper head was reduced to the stent's outer diameter. Then the balloonwas inflated to stent's outer diameter or the crimper's inner diameterat the pressure of 30 psi. The stent was crimped down further underpressure or release pressure at a slow rate and then held at targetcrimping diameter for certain time without balloon pressure present.

Both groups were measured by Instron Tester. Bottom grip on the Instronheld the balloons below the stent and the upper grip held a stentsection on the balloons. The device was used to pull the stents awayfrom the balloons by moving the upper grip in an upwards direction. Theforce was measured when the stents moved at least of 1 mm from theoriginal location. FIG. 5 illustrates the result.

EXAMPLE 2.

A stent can be mounted on a balloon, followed by inflating the balloonto an inner diameter of the stent. Crimp to intermediate diameter,between original diameter of the stent and final, desired diameter ofthe stent. The balloon can then be deflated by pulling vacuum onballoon, for example. Next, the balloon can be inflated to anintermediate diameter (diameter is controlled by position of crimpinghead). Crimp to final, desired diameter. This method can provide supportto the stent during the initial crimping process and reduces crimpingdefects during the manufacturing process.

While particular embodiments of the present invention have beendescribed, it will be obvious to those skilled in the art that changesand modifications can be made without departing from the spirit andscope of the teachings and embodiments of this invention. Therefore, theappended claims are to encompass within their scope all such changes andmodifications as fall within the true spirit of this invention.

1. A method of crimping a stent on a balloon, comprising the followingacts in the order as listed: (a) providing a poly (L-lactide) stentdisposed over a balloon in an inflated configuration, the balloon beinginflated by a fluid at a temperature of a glass transition temperature(T_(g)) of the poly (L-lactide) stent; (b) crimping the stent to a firstreduced diameter; (c) at least partially deflating the balloon; (d)inflating the balloon to at least an inner diameter of the stent; and(e) crimping the stent to a second reduced diameter.
 2. The method ofclaim 1, wherein the second reduced diameter is a final crimpeddiameter.
 3. The method of claim 2, additionally comprising, followingact (e): (f) at least partially deflating the balloon; followed by (g)inflating the balloon to at least an inner diameter of the stent;followed by (e) crimping the stent to a third reduced diameter.
 4. Themethod of claim 3, wherein the third reduced diameter is a final crimpeddiameter.
 5. A stent-balloon catheter assembly made in accordance withthe method of claim
 1. 6. The method of claim 1, wherein a balloonsoftening fluid is applied to the balloon.
 7. The method of claim 1,wherein a solvent is applied to the balloon surface.
 8. The method ofclaim 1, wherein the crimping is performed using a crimper.
 9. Themethod of claim 8, wherein the crimper is an iris crimper.
 10. Themethod of claim 8, wherein the crimper includes jaws configured to moveinward.
 11. The method of claim 1, wherein the crimping of steps (b) and(d) include radially compressing the stent between jaws of a crimper.12. The method of claim 1, wherein the stent is in a crimping device forsteps (b) and (d).
 13. The method of claim 12, wherein the balloon isinflated before being placed in the crimping device.
 14. The method ofclaim 1, wherein prior to step (c) the balloon has a crimp inflationstate that is greater than a collapsed state of the balloon.
 15. Themethod of claim 1, wherein subsequent to crimping the stent to thesecond reduced diameter a membrane or wall of the balloon is pinched orwedged between structural elements of the stent.
 16. The method of claim1, wherein during at least step (b) the pressure in the balloon iscontrollably released by a valve.